6533b7d3fe1ef96bd1261509

RESEARCH PRODUCT

Anti-fibrotic therapy: lost in translation?

Detlef SchuppanDetlef SchuppanMassimo PinzaniMassimo Pinzani

subject

Liver Cirrhosismedicine.medical_specialtyCirrhosisPlacebo-controlled studyAutoimmune hepatitisChronic liver diseaseGastroenterologyPrimary sclerosing cholangitisTranslational Research BiomedicalPrimary biliary cirrhosisFibrosisInternal medicinemedicineAnimalsHumansIntensive care medicineHepatologymedicine.diagnostic_testbusiness.industryPatient Selectionmedicine.diseaseMagnetic Resonance ImagingDisease Models AnimalLiver biopsybusinessBiomarkers

description

While preclinical development of potential anti-fibrotics is far advanced, with numerous pharmacological targets and promising agents, almost none has entered clinical validation. Reasons are manifold, including the usually slow progression of liver fibrosis, requiring high numbers of well-stratified patients undergoing long-term treatment when conventional liver biopsy based parameters or hard liver-related endpoints are used. Importantly, there is a notorious lack of sensitive and specific surrogate markers or imaging technologies for liver fibrosis progression or regression that would permit a rapid clinical screening for potential anti-fibrotics. Nonetheless, in view of an urgent need for anti-fibrotics that positively impact morbidity and mortality from chronic liver diseases, the field is now moving more quickly towards clinical translation. This development is driven by thoughtful preclinical validation, a better study design and improved surrogate readouts using currently available methodologies. Moreover, upcoming novel biomarkers and imaging technologies will soon permit a more exact and efficient assessment of fibrosis progression and regression.

10.1016/s0168-8278(12)60008-7https://pubmed.ncbi.nlm.nih.gov/22300467